Establishment of Myocardial Regeneration Therapy Using Small Molecule-Responsive Artificial Receptors For Growth Factor Signal Transduction

使用小分子响应人工受体进行生长因子信号转导建立心肌再生疗法

• 批准号: 24659388
• 负责人: KAWAMURA Teruhisa
• 金额: $ 2.33万
• 依托单位: Ritsumeikan University (2013)Kyoto University (2012)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659388/
• 关键词: 再生医学; 幹細胞生物学; 人工受容体; 体細胞初期化

Signal transduction from Wnt ligands or Granulocyte Colony Stimulating factor (G-CSF) links to pathways involved in myocardial cell differentiation or cell survival from external stress stimuli. To control these signals in pluripotent stem cells is expected to improve the efficiency for cell survival after implantation as well as for myocardial cell induction. Then, we attempted to generate small molecule-responsive artificial receptors that can activate signal pathways, in the absence of Wnt3a or G-CSF. In the present research project, we constructed chimeric receptors in which single-chain Fv of anti-fluorescein (FL) antibody was tethered to transmembrane/cytoplasmic domains of the receptor for Wnt3a or G-CSF. Mouse ES cells or iPS cells transduced with these chimeric receptors are able to activate the signals in response to FL-conjugated BSA (BSA-FL) as a cognate ligand, and show increased efficiency for myocardial cell differentiation when they are stimulated with BSA-FL.

来自Wnt配体或粒细胞集落刺激因子（G-CSF）的信号转导与参与心肌细胞分化或来自外部应激刺激的细胞存活的途径有关。控制多能干细胞中的这些信号有望提高植入后细胞存活以及心肌细胞诱导的效率。然后，我们试图在Wnt 3a或G-CSF不存在的情况下产生可以激活信号通路的小分子响应性人工受体。在本研究项目中，我们构建了嵌合受体，其中抗荧光素（FL）抗体的单链Fv连接到Wnt 3a或G-CSF受体的跨膜/胞质结构域。用这些嵌合受体转导的小鼠ES细胞或iPS细胞能够激活响应于FL缀合的BSA（BSA-FL）作为同源配体的信号，并且当用BSA-FL刺激时，显示出增加的心肌细胞分化效率。

项目成果

Functional regulation of Wnt3a signaling for an efficient and economical production of cardiac myocytes from mouse ES cells using chimeric receptors for Wnt3a.

使用 Wnt3a 嵌合受体对 Wnt3a 信号传导进行功能调节，以有效且经济地从小鼠 ES 细胞中产生心肌细胞。

• 作者: Sogo T;Shigeno A;Baba A;Hasegawa K;Kawahara M;Nagamune T;Kawamura T.
• 通讯作者: Kawamura T.

Foxd1 is a mediator and indicator of the cell reprogramming process

• DOI: 10.1038/ncomms4197
• 发表时间: 2014-02-01
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Koga, Makito;Matsuda, Mitsuhiro;Ebisuya, Miki
• 通讯作者: Ebisuya, Miki

医学のあゆみ

医学史

• 发表时间: 2022
• 作者: 藤田陽子;野田岳志
• 通讯作者: 野田岳志

体細胞初期化と幹細胞分子の分子機構の解明とその再生医学への応用

阐明体细胞重编程和干细胞分子的分子机制及其在再生医学中的应用

• 作者: Sogo T;Shigeno A;Baba A;Hasegawa K;Kawahara M;Nagamune T;Kawamura T.;川村晃久
• 通讯作者: 川村晃久

Functional regulation of Wnt3a signaling for an efficient and economical production of cardiac myocytes from mouse ES cells using chimeric receptors for Wnt3a

使用 Wnt3a 嵌合受体对 Wnt3a 信号传导进行功能调节，以高效、经济地从小鼠 ES 细胞中产生心肌细胞

• 发表时间: 2013
• 作者: Sogo T;Shigeno A;Baba A;Hasegawa K;Kawahara M;Nagamune T;Kawamura T.
• 通讯作者: Kawamura T.